Method of synthesis of dialkyl alphaketoglutarate from alkyl 2-furoate



United States Patent METHOD OF SYNTHESIS OF DIALKYL ALPHA- KETOGLUTARATE FROM ALKYL' Z-FUROATE Masno Murakami, 1-39, 3-Cho, Sekimori-cho, Suma-ku, and Saburo Senoh, 274 Mori, Motoyama-cho, Nada-kn, both of Kobe-shi, Hyogo-ken, Japan The invention described herein pertains to a method of synthesis of dialkyl alpha-ketoglutarate, featuring the cleavage of the furan ring of alkyl Z-furoate by chlorine and a lower alkanol.

The object of this invention is to provide an improved method or procedure for facilitating the manufacturing of dialkyl alpha-ketoglutarates which can be used as a raw material for the preparation of glutamic acid or various processes involved in the manufacture of the said compound are short and the reaction conditions can readily be attained.

Example butenalpha-carboxylate bis-2,4-dinitrophenylhydrazone 45 (C19H16O10N3), M.P. 241-242 C. (dec.) with high yields.

Its analytical results are as follows:

0 (Per- H (Per- N (Percent) cent) cent) A1181. Cale'd f0! UmHmOmNs 44. 19 3.12 21. 70 Found 44.46 p 3.16 21.83

The reaction mixture containing the 2,5-diethoxy-2,5- dihydro-2-furoate was then heated on a water bath under reflux conditions for several hours to convert the 2,5- diethoxy-2,5-dihydro-2-furoate to diethyl alpha-ketoglutarate. .In order to prove that diethyl alphaketoglutarate was actually formed, a portion of this final 5 reaction mixture was treated with a solution of 2,4-

dinitrophenylhydrazine sulfate in ethanol, thus obtaining diethyl alpha-ketoglutarate 2,4-d.initrophenylhydrazone, M.P. 8889 C., in high yields. Its analysis is given below:

0 (Per- H (Per- N (Percent) cent) cent) A1181. Galc'd for CH1aOaN4 47. 12 4. 75 14. 66 16 Found 47. 13 4. 76 14. 73

If desired, the reaction mixture containing the 2,5- diethoxy 2,S-dihydro-Z-furoate can be saturated with hydrogen chloride gas before heating to form the diethyl 20 alpha-ketoglutarate.

It is also possible to obtain diethyl alpha-ketoglutarate, B.P. 1l6-ll8 C./4 mm., in a theoretical yield of over 70% by distilling under vacuum the residue obtained after removing the solvent from the reaction mixture containing the diethyl'alpha-ketoglutarate.

When methyl 2-furoate and methanol are used instead of the ethyl derivative and ethanol used in this case, dimethyl alpha-ketoglutarate is obtained in approximately the same high yield, Since it is possible to see numerous variations of the procedures given above without altering the feature and principle of the said invention, thesaid invention is by the scope claimed hereafter. 85 What we claim is: I

A method for the production of a lower dialkyl a1pha ketoglutarate consisting essentially of reacting a lower alkyl-2-furoate with a lower' alkanol and chlorine at a temperature not exceeding room temperature, and then 40 forming said alpha-ketoglutarate by heating the resulting reaction mixture under reflux conditions. 7

References Cited in the file of this patent UNITED STATES PATENTS 2,436,532 Singleton Feb. 24, 1948 2,475,097 Jones July 5, 1949 2,515,304 Jones July 18, 1950 OTHER REFERENCES Dunlop et al.: The Furans (1953), pages 390-4, 496. Hachihama et al.: Chem. Abs. 50, 12015a (1956) (J. Chem. Soc. Japan, Ind. Chem. Sec. 58, 806 (1955).

Murakami et al.: Chem.'Abs. 51, 5745-6747 (1957) (Mem. Inst; Sci. Ind. Research, Osaka Univ., 13, 173- Patented July 26,1960

no means avoided by any minor changes employed within 

